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Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.

ABSTRACT: ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. In contrast to earlier results, we found SNF2L to be broadly expressed in primary human tissues. Depletion of SNF2L in HeLa cells led to enhanced proliferation and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. Accordingly, high levels of SNF2L expression in normal melanocytes contrast with undetectable expression in malignant melanoma. In summary, our data document an inverse relationship between SNF2L expression and features characteristic of malignant cells.

SUBMITTER: Eckey M

PROVIDER: S-EPMC3434487 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.

Eckey Maren M Kuphal Silke S Straub Tobias T Rümmele Petra P Kremmer Elisabeth E Bosserhoff Anja K AK Becker Peter B PB

Molecular and cellular biology 20120416 13

ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes i ...[more]

PMID: 22508985

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Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.

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Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.

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